Vitamin D Deficiency among Patients with Tuberculosis: a Cross-Sectional Study in Iranian-Azari Population.

Background: Vitamin D deficiency or insufficiency has been conducted with increased risk for tuberculosis (TB). Despite this association, discrepancies exist among different studies in different regions. The aim of this study was to evaluate the prevalence of vitamin D deficiency and its predictors in tuberculosis among the Iranian-Azari population. Materials and Methods: A total of 60 participants were enrolled in this study, 30 of which were newly diagnosed TB patients and 30 were healthy volunteers. At least two serum samples were collected, the first sample before the start of anti-TB treatment and the second sample 3 months after the effective treatment. Results: The prevalence of vitamin D deficiency (25 patients vs. 2 healthy individuals; P<0.001) and serum levels of the vitamin D (22.66±15.17 vs. 73.03±25.6 ng/mL; P<0.001) were significantly higher in patients with TB than healthy subjects. Likewise, the prevalence of vitamin D deficiency in the extrapulmonary TB group was higher than that of the pulmonary TB, but this difference was not statistically significant (P=0 .397). Moreover, there was no significant difference between mean levels of vitamin D in patients with tuberculosis before and after treatment (P = 0.787). Linear regression analysis showed there was no significant relationship between vitamin D levels after treatment and age, gender, body site of tuberculosis, and vitamin D levels before treatment, P≥0.68. Conclusion: Vitamin D deficiency is higher in patients with tuberculosis than healthy individuals.


INTRODUCTION
Tuberculosis (TB) is a major global health problem and has been reported to cause approximately 1.4 million deaths a year (1). In addition to its negative impacts on the quality of life, it imposes a high burden on the health system (2,3). It has been estimated that about one-third of the world's population is infected with latent Mycobacterium tuberculosis (4), 10% of which will develop the active disease (5). Despite the decline in mortality and morbidity of the disease in recent decades, TB remains a main global public health threat (6,7).
Several factors are considered as risk factors for tuberculosis; however, one responsible element may be vitamin D deficiency. From the past, vitamin D and sunlight were used to treat tuberculosis. Now, there is growing proof that vitamin D increases anti-mycobacterial protection (8,9). Vitamin D, a regulator of macrophage function, can stimulate human anti-mycobacterial activity. Many observations have shown that vitamin D deficiency is related to a higher risk of tuberculosis infection. In the first place, tuberculosis tends to occur during the cold seasons at a time when vitamin synthesis from sunlight in the skin cells is minimized and serum vitamin D levels are lower. In the next step, untreated TB patients, especially those who live in temperate climates, have lower serum vitamin D levels than healthy individuals. In addition, the prevalence of tuberculosis is higher among people such as the elderly and uremic patients who have lower serum vitamin D levels (10,11).
The effects of vitamin D on the immune system is due to its role in the innate immunity system (12). Moreover, CD4+ and CD8+ T cells, by producing chemokines, such as CC and CXC, have protective effects against TB infection (13). The antimicrobial activity of TLRs depends on the presence of vitamin D (14). This vitamin works by binding to its nucleus receptor in the target cell. Therefore, vitamin D deficiency and any structural and functional disorders in its receptor can lead to an impairment of host immunity against bacillus tuberculosis (15). 25-hydroxyvitamin D is a biomarker for determining the vitamin D levels of the human body (16). Studies have shown that vitamin D enhances phagocytosis of macrophages and the production of Cathelicidin antimicrobial peptide and accelerates M. tuberculosis intracellular death (17). Studies have shown that there is a relationship between the deficiency of this vitamin and TB (18,19). Also, an antimicrobial pathway depend on INF-γ in macrophages is associated with appropriate serum levels of vitamin D (20). The vitamin D levels in patients with TB have been controversial in previous studies. Some studies have reported the reduction of vitamin D levels in patient with TB compared to the healthy individuals (21,22), while others fail to detect these findings (23). Levels of vitamin D vary among populations and affected by various racial, cultural and geographical causes (24,25). Hence, the aim of this study was to evaluate the level of vitamin D and its confounding factors in patients with TB and healthy individuals in Iranian-Azari population. Patients were informed about their inclusion in the study and signed a consent form. Patients information associated with serum vitamin D levels, such as age, gender, history of comorbidity and history of drug usage were collected.

MATERIALS AND METHODS
Serum samples were collected between 7 and 9 AM after at least 12 h night fasting. In each patient, at least two vitamin D serum samples were determined and this included a sample before the onset of anti TB treatment In this study, no significant relationship was found between age and gender with vitamin D levels. In contrast, several studies from Pakistan (38) and Ethiopia (30) showed a higher level of vitamin D deficiency in the female gender. This might be ascribed to pregnancy and inadequate sunlight exposure. Some studies performed on an African population showed that aging was significantly associated with vitamin D deficiency (30,39).
This cross-sectional study had some limitations. The sample size was not large enough; however, all the newly diagnosed patients were studied in one year. Furthermore, dietary intake, clothing coverage, the seasons' effects, and residences in the urban or rural were not considered in our study. However, our study was the first report from the

CONCLUSION
The prevalence of vitamin D deficiency in patients was significantly higher than the control group. The mean of serum vitamin D levels in patients with TB before treatment was significantly lower than that of the controls, and vitamin D levels in tuberculosis patients reduced after treatment. In this study, no significant relationship was found between age and gender with vitamin D levels.

ACKNOWLEDGEMENT
The authors wish to thank the participants for their cooperation.

CONFLICTS OF INTERESTS
There are no conflicts of interest.